Cytosolic Cl- Affects the Anticancer Activity of Paclitaxel in the Gastric Cancer Cell Line, MKN28 Cell

Background/Aims: Our previous study revealed that cytosolic Cl- affected neurite elongation promoted via assembly of microtubule in rat pheochromocytoma PC12D cells and Cl-–induced blockade of intrinsic GTPase enhanced tubulin polymerization in vitro. Paclitaxel (PTX) is a microtubule-targeted chemotherapeutic drug and stabilizes microtubules resulting in mainly blockade of mitosis at the metaphase-anaphase transition and induction of apoptosis. In the present study, we tried to clarify whether the cytosolic Cl- affected PTX ability to inhibit cell growth in the gastric cancer cell line, MKN28. Methods: To clarify the cytosolic Cl- action on PTX-induced cell death and metaphase-anaphase transition in the gastric cancer cell line, MKN28 cell, and PTX-induced tubulin polymerization, we performed cell proliferation assay, cytosolic Cl- concentration measurement, immunofluorescence microscopy, and in vitro tubulin polymerization assay. Results: The decline of cytosolic Cl- weakened the cytotoxic effect of PTX on cell proliferation of MKN28 cells, which could pass through the metaphase-anaphase transition. Moreover, in vitro PTX-induced tubulin polymerization was diminished under the low Cl- condition. Conclusions: Our results strongly suggest that the upregulation of cytosolic Cl- concentration would enhance the antitumor effect of PTX, and that the cytosolic Cl- would be one of the key targets for anti-cancer therapy.

[1]  T. Bek,et al.  Reduced Expression of Cytoskeletal and Extracellular Matrix Genes in Human Adult Retinal Pigment Epithelium Cells Exposed to Simulated Microgravity , 2016, Cellular Physiology and Biochemistry.

[2]  Akiyuki Taruno,et al.  Quercetin is a Useful Medicinal Compound Showing Various Actions Including Control of Blood Pressure, Neurite Elongation and Epithelial Ion Transport. , 2016, Current medicinal chemistry.

[3]  K. Kamijo,et al.  ERK Plays a Role in Chromosome Alignment and Participates in M‐Phase Progression , 2016, Journal of cellular biochemistry.

[4]  S. Yuspa,et al.  Chloride channels in cancer: Focus on chloride intracellular channel 1 and 4 (CLIC1 AND CLIC4) proteins in tumor development and as novel therapeutic targets. , 2015, Biochimica et biophysica acta.

[5]  Paolo Meda,et al.  Ionic imbalance, in addition to molecular crowding, abates cytoskeletal dynamics and vesicle motility during hypertonic stress , 2015, Proceedings of the National Academy of Sciences.

[6]  Anmin Liu,et al.  Fasudil Stimulates Neurite Outgrowth and Promotes Differentiation in C17.2 Neural Stem Cells by Modulating Notch Signalling but not Autophagy , 2015, Cellular Physiology and Biochemistry.

[7]  He Huang,et al.  Ketamine Interferes with the Proliferation and Differentiation of Neural Stem Cells in the Subventricular Zone of Neonatal Rats , 2015, Cellular Physiology and Biochemistry.

[8]  Wan Yu,et al.  MiR-133b Promotes Neurite Outgrowth by Targeting RhoA Expression , 2015, Cellular Physiology and Biochemistry.

[9]  Y. Marunaka,et al.  Insulin is involved in transcriptional regulation of NKCC and the CFTR Cl− channel through PI3K activation and ERK inactivation in renal epithelial cells , 2014, The Journal of Physiological Sciences.

[10]  Linyan Zhu,et al.  Functional expression of chloride channels and their roles in the cell cycle and cell proliferation in highly differentiated nasopharyngeal carcinoma cells , 2014, Physiological reports.

[11]  K. Hamilton,et al.  Distinct Action of Flavonoids, Myricetin and Quercetin, on Epithelial Cl− Secretion: Useful Tools as Regulators of Cl− Secretion , 2014, BioMed research international.

[12]  Y. Nakayama,et al.  Genistein Induces Cytokinesis Failure Through RhoA Delocalization and Anaphase Chromosome Bridging , 2014, Journal of cellular biochemistry.

[13]  D. Ichikawa,et al.  A regulatory role of K(+)-Cl(-) cotransporter in the cell cycle progression of breast cancer MDA-MB-231 cells. , 2013, Archives of biochemistry and biophysics.

[14]  Haifeng Zhang,et al.  The ClC-3 chloride channel associated with microtubules is a target of paclitaxel in its induced-apoptosis , 2013, Scientific Reports.

[15]  I. Novak,et al.  Cell volume regulation in epithelial physiology and cancer , 2013, Front. Physiol..

[16]  Anne Straube,et al.  Mechanical properties of doubly stabilized microtubule filaments. , 2013, Biophysical journal.

[17]  J. Díaz,et al.  The binding sites of microtubule-stabilizing agents. , 2013, Chemistry & biology.

[18]  T. Terasaki,et al.  Identification of Transporters Associated with Etoposide Sensitivity of Stomach Cancer Cell Lines and Methotrexate Sensitivity of Breast Cancer Cell Lines by Quantitative Targeted Absolute Proteomics , 2013, Molecular Pharmacology.

[19]  Y. Marunaka,et al.  Enhancement of tubulin polymerization by Cl(-)-induced blockade of intrinsic GTPase. , 2012, Biochemical and biophysical research communications.

[20]  H. Sakaguchi,et al.  K+-Cl-Cotransporter 1 (KCC1) Negatively Regulates NGF-induced Neurite Outgrowth in PC12 Cells , 2012, Cellular Physiology and Biochemistry.

[21]  Akiyuki Taruno,et al.  Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel , 2011, Journal of biomedicine & biotechnology.

[22]  Y. Marunaka,et al.  Genistein enhances the NGF-induced neurite outgrowth. , 2011, Biomedical research.

[23]  Y. Marunaka,et al.  Quercetin Stimulates NGF-induced Neurite Outgrowth in PC12 Cells via Activation of Na+/K+/2Cl- Cotransporter , 2011, Cellular Physiology and Biochemistry.

[24]  T. Miki,et al.  Chloride Ion Modulates Cell Proliferation of Human Androgen-independent Prostatic Cancer Cell , 2010, Cellular Physiology and Biochemistry.

[25]  Matthew Mirigian,et al.  Mechanics of microtubules. , 2010, Journal of biomechanics.

[26]  M. Niemi,et al.  Impact of OATP transporters on pharmacokinetics , 2009, British journal of pharmacology.

[27]  R. Wade,et al.  On and Around Microtubules: An Overview , 2009, Molecular biotechnology.

[28]  Yatin R. Gokarn,et al.  Ion‐specific modulation of protein interactions: Anion‐induced, reversible oligomerization of a fusion protein , 2008, Protein science : a publication of the Protein Society.

[29]  M. Rasenick,et al.  Submembraneous microtubule cytoskeleton: regulation of microtubule assembly by heterotrimeric G proteins , 2008, The FEBS journal.

[30]  Barbara McGrogan,et al.  Taxanes, microtubules and chemoresistant breast cancer. , 2008, Biochimica et biophysica acta.

[31]  Atsushi Shiozaki,et al.  Chloride ions control the G1/S cell-cycle checkpoint by regulating the expression of p21 through a p53-independent pathway in human gastric cancer cells. , 2008, Biochemical and biophysical research communications.

[32]  T. Kubo,et al.  Chloride-dependent acceleration of cell cycle via modulation of Rb and cdc2 in osteoblastic cells. , 2007, Biochemical and biophysical research communications.

[33]  P. Dri,et al.  Chloride Movements in Human Neutrophils during Phagocytosis: Characterization and Relationship to Granule Release , 2007, The Journal of Immunology.

[34]  Y. Marunaka,et al.  Essential role of NKCC1 in NGF-induced neurite outgrowth. , 2007, Biochemical and biophysical research communications.

[35]  Mikko Niemi,et al.  Role of OATP transporters in the disposition of drugs. , 2007, Pharmacogenomics.

[36]  H. Kato,et al.  Modulation of drug-stimulated ATPase activity of human MDR1/P-glycoprotein by cholesterol. , 2007, The Biochemical journal.

[37]  A. Shiozaki,et al.  Furosemide, a blocker of Na+/K+/2Cl- cotransporter, diminishes proliferation of poorly differentiated human gastric cancer cells by affecting G0/G1 state. , 2006, The journal of physiological sciences : JPS.

[38]  Deepak Sampath,et al.  Preclinical Pharmacologic Evaluation of MST-997, an Orally Active Taxane with Superior In vitro and In vivo Efficacy in Paclitaxel- and Docetaxel-Resistant Tumor Models , 2006, Clinical Cancer Research.

[39]  E. Pasquier,et al.  Understanding microtubule dynamics for improved cancer therapy , 2005, Cellular and Molecular Life Sciences CMLS.

[40]  H. Schatten,et al.  Cell cycle-dependent localization and possible roles of the small GTPase Ran in mouse oocyte maturation, fertilization and early cleavage. , 2005, Reproduction.

[41]  Toshinori Yamamoto,et al.  Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]) , 2005, The Journal of pharmacy and pharmacology.

[42]  A. Sparreboom,et al.  Identification of OATP1B3 as a high-affinity hepatocellular transporter of paclitaxel , 2005, Cancer biology & therapy.

[43]  D. Kingston,et al.  Syntheses and bioactivities of macrocyclic paclitaxel bis-lactones. , 2004, Bioorganic & medicinal chemistry.

[44]  D. Eaton,et al.  Involvement of cytosolic Cl− in osmoregulation of α-ENaC gene expression , 2004 .

[45]  D. Hallifax,et al.  Predicting P-Glycoprotein Effects on Oral Absorption: Correlation of Transport in Caco-2 with Drug Pharmacokinetics in Wild-Type and mdr1a(-/-) Mice in Vivo , 2004, Pharmaceutical Research.

[46]  C. Inagaki,et al.  Expression and roles of Cl- channel ClC-5 in cell cycles of myeloid cells. , 2004, Biochemical and biophysical research communications.

[47]  M. Jordan,et al.  Microtubules as a target for anticancer drugs , 2004, Nature Reviews Cancer.

[48]  C. Inagaki,et al.  Suppression of cell proliferation with induction of p21 by Cl(-) channel blockers in human leukemic cells. , 2004, European journal of pharmacology.

[49]  C. Higgins,et al.  Cell volume regulation and swelling-activated chloride channels. , 2003, Biochimica et biophysica acta.

[50]  Susan Band Horwitz,et al.  Mechanisms of Taxol resistance related to microtubules , 2003, Oncogene.

[51]  K. Shedden,et al.  Analysis of cell-cycle-specific gene expression in human cells as determined by microarrays and double-thymidine block synchronization , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[52]  M. Rasenick,et al.  G Protein α Subunits Activate Tubulin GTPase and Modulate Microtubule Polymerization Dynamics* , 1999, The Journal of Biological Chemistry.

[53]  P. Dri,et al.  Triggering of chloride ion efflux from human neutrophils as a novel function of leukocyte beta 2 integrins: relationship with spreading and activation of the respiratory burst. , 1999, Journal of immunology.

[54]  P. Dri,et al.  Chloride ion efflux regulates adherence, spreading, and respiratory burst of neutrophils stimulated by tumor necrosis factor-alpha (TNF) on biologic surfaces , 1996, The Journal of cell biology.

[55]  M. Jordan,et al.  Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[56]  E. Hamel,et al.  Guanosine 5'-O-(3-thiotriphosphate), a potent nucleotide inhibitor of microtubule assembly. , 1984, The Journal of biological chemistry.

[57]  P. Schiff,et al.  Taxol assembles tubulin in the absence of exogenous guanosine 5'-triphosphate or microtubule-associated proteins. , 1981, Biochemistry.

[58]  P. Schiff,et al.  Taxol stabilizes microtubules in mouse fibroblast cells. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[59]  P. Schiff,et al.  Promotion of microtubule assembly in vitro by taxol , 1979, Nature.

[60]  C. Cantor,et al.  Turbidimetric studies of the in vitro assembly and disassembly of porcine neurotubules. , 1974, Journal of molecular biology.

[61]  D. Prescott,et al.  An evaluation of the double thymidine block for synchronizing mammalian cells at the G1-S border. , 1971, Experimental cell research.

[62]  大澤 るみ.  Intracellular chloride regulates cell proliferation through the activation of stress-activated protein kinases in MKN28 human gastric cancer cells , 2010 .

[63]  D. Kingston,et al.  Promotion of tubulin assembly by poorly soluble taxol analogs. , 2007, Analytical biochemistry.

[64]  D. Eaton,et al.  Involvement of cytosolic Cl- in osmoregulation of alpha-ENaC gene expression. , 2004, American journal of physiology. Renal physiology.

[65]  M. Gottesman,et al.  Multidrug resistance in cancer: role of ATP–dependent transporters , 2002, Nature Reviews Cancer.

[66]  M. Gottesman.  Mechanisms of cancer drug resistance. , 2002, Annual review of medicine.

[67]  M. Rasenick,et al.  G protein alpha subunits activate tubulin GTPase and modulate microtubule polymerization dynamics. , 1999, The Journal of biological chemistry.

[68]  E. Nogales,et al.  Structure of the alpha beta tubulin dimer by electron crystallography. , 1998, Nature.